PT  - JOURNAL ARTICLE
AU  - Michael J. Saganich
AU  - Brock E. Schroeder
AU  - Veronica Galvan
AU  - Dale E. Bredesen
AU  - Edward H. Koo
AU  - Stephen F. Heinemann
TI  - Deficits in Synaptic Transmission and Learning in Amyloid Precursor Protein (APP) Transgenic Mice Require C-Terminal Cleavage of APP
AID  - 10.1523/JNEUROSCI.4180-06.2006
DP  - 2006 Dec 27
TA  - The Journal of Neuroscience
PG  - 13428--13436
VI  - 26
IP  - 52
4099  - http://www.jneurosci.org/content/26/52/13428.short
4100  - http://www.jneurosci.org/content/26/52/13428.full
SO  - J. Neurosci.2006 Dec 27; 26
AB  - Synaptic dysfunction has been shown to be one of the earliest correlates of disease progression in animal models of Alzheimer's disease. Amyloid-β protein (Aβ) is thought to play an important role in disease-related synaptic dysfunction, but the mechanism by which Aβ leads to synaptic dysfunction is not understood. Here we describe evidence that cleavage of APP in the C terminus may be necessary for the deficits present in APP transgenic mice. In APP transgenic mice with a mutated cleavage site at amino acid 664, normal synaptic transmission, synaptic plasticity, and learning were maintained despite the presence of elevated levels of APP, Aβ42, and even plaque accumulation. These results indicate that cleavage of APP may play a critical role in the development of synaptic and behavioral dysfunction in APP transgenic mice.